The molecular basis of E. coli colonization of the large intestine will be investigated using a mouse model. Mutants of normal human fecal strains of E. coli, which have an impaired ability to colonize the large intestine as a result of limited genetic manipulation and which possess well-defined altered surface properties will be used to investigate microbial interaction with the mucous gel blanket of the large intestine. Bacterial binding of soluble mucous gel glycoproteins and bacterial adhesion to immobilized mucous gel glycoproteins will be assessed in vitro and compared to in vivo colonizing ability. The bacterial surface components (adhesins) and individual mucous gel components (receptors) involved in the interaction will be isolated and biochemically characterized. The overall objective of the proposed research is to characterize bacterial-mucous gel interactions and to clarify the role of the mucous gel in E. coli colonization of the large intestine.